PROJECT SUMMARY - OVERALL Building on a 26-year history, the Environmental Health Sciences Research Center (EHSRC) will advance and translate cutting edge research that addresses environmental health problems across the urban-rural continuum. Rural America faces unique environmental challenges from exposures to farm chemicals, air and water pollution from livestock and agricultural production, rural manufacturing, and the green energy economy. The EHSRC is at the forefront of research in rural environmental health, determining the role of the microbiome in environmental lung disease; elucidating novel pathways of oxidative stress and innate immunity; investigating epigenetic mechanisms of cell alterations; discovering therapeutic modalities to treat environmental disease; and characterizing adverse outcome pathways of engineered nanomaterials, pesticides and other xenobiotics. The EHSRC vision is to be the primary environmental health sciences (EHS) resource for improving the health of rural residents by stimulating and translating innovative EHS research. This is accomplished by gaining new insights into rural exposures; population health; susceptibilities; and pathways of toxicity and repair; and then translating these insights to medicine, public health practice and regulatory policy. Center goals are to: 1) Develop, support and expand innovative interdisciplinary EHS research in key Thematic Areas; 2) Recruit, mentor and nurture talented new and mid-level investigators in EHS; and 3) Engage with communities and policy makers to translate research findings toward improving the health and environment of rural people in the Midwest and the nation. The interdisciplinary research of the EHSRC is organized around Thematic Areas which are: Inflammation and Innate Immunity, Oxidative Stress and Metabolism, Nanotoxicology, and Environmental Disease and Population Health. Three EHSRC facility cores: Integrative Health Sciences Facility, Pulmonary Toxicology Facility, and Environmental Modeling & Exposure Assessment Facility, provide cutting edge services, state-of-the-art equipment and support the authentication of key biological and chemical resources. An Administrative Core provides transformative leadership, leverages institutional support and manages highly effective Pilot Grant and Career Development Programs that provide resources and mentoring to advance the careers of promising and diverse young investigators. The Community Outreach and Engagement Core engages stakeholders in multidirectional communications to ensure relevance of EHSRC research and to translate research findings to environmental public health. Lastly, the EHSRC responds to environmental disasters disseminating accurate and timely information and collecting real-time data on the severity of the disaster and effectiveness of the response.